In this project we propose to study health effects of chlorinated and pyrethroid pesticides. The compounds proposed for study are: chlordane components, mirex-kepone, TCDD (dioxin), fenothrin and permethrin. DDT and allethrin will be used as the standard chemicals for each group of pesticides. These are the chemicals which have already caused serious environmental contamination, or the ones which are being newly developed and are yet to be studied for their toxicological properties. Their effects will be examined in two important organs, the nervous system and the liver. In addition, in some cases the kidney will be examined. These are the organs which show very high sensitivities toward these chemicals. From the enzymatic viewpoint ATPases will be examined as the key target systems, since they play such vital roles in each organ in addition to their sensitivities to chlorinated and pyrethroid pesticides. Those ATPases which show special susceptibilities to each pesticidal chemical will be characterized and its implication in nerve and liver function (e.g. effects on bile excretion) will be studied. In the case of relatively labile chemicals (e.g. chlordane components) some metabolic studies will be conducted. For instance, the human liver shows a low metabolic activity toward trans-nonachlor as compared to that by the rat liver. This species difference in the rate of dechlorination to form relatively labile trans-chlordane could prove to be a very important factor in comparative toxicology. We also propose to study the "induction" phenomenon caused by these chemicals in the rat liver. Induction is one of the most sensitive biochemical lesions. It can take place even in the range of the concentration of pesticides which are often observed in animal samples in nature. The pattern of induction caused by these chemicals is by no means uniform. Different groups of chemicals induce different types of cytochromes, enzymes, and proteins. Here we will study the differences in induction patterns among these chemicals as compared to other standard inducing agents such as 3-methylcholanthrin, phenobarbital and testosterone to define the health effects of each pesticidal chemical.